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Uri Soiberman, Siva Pramodh Kambhampati, Manoj K. Mishra, Samuel C Yiu, Abdul Elah Al Towerki, Walter J. Stark, Rangaramanujam M. Kannan; Subconjunctival dendrimer-drug therapy for the treatment of corneal inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5035.
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To assess whether subconjunctivally administered dendrimers target activated corneal macrophages, and also whether subconjunctival dendrimer-dexamethasone (D-Dex) conjugate is efficacious in the treatment of corneal alkali burn.
A rat animal model of corneal alkali burn was used by exposure to 1N NaOH solution. 48 hours following the alkali burn, subconjunctival treatment was administered with either dendrimer-Cy5 (D-Cy5; to assess corneal macrophage uptake), or D-Dex (therapy). The rats were assessed for corneal edema, corneal opacity and development of corneal neovascularization (NV). Central corneal thickness (CCT) was assessed with anterior segment optical coherence tomography (OCT). The rats were sacrificed 7 days after the alkali burn and the corneas were cross sectioned and then prepared for histological assessment and confocal microscopy.
Alkali burn led to increased macrophage accumulation, corneal thickness, opacity and edema in the central cornea. D-Cy5 was selectively co-localized with the corneal macrophages in the central cornea. D-Dex treatment resulted in favorable outcomes with reduced CCT and edema, fewer central corneal macrophages and improved corneal clarity compared to untreated controls. Corneal NV was assessed one week following alkali burn: the D-Dex treated eyes had reduced corneal NV (1.5±1.2 quadrants) as opposed to untreated eyes (4±0 quadrants) (p=0.02). Eyes treated with D-Dex did not have elevated intraocular pressures compared with controls.
This short-term pilot study conducted in rats demonstrates that dendrimers can target macrophages and be retained in them for up to one week following alkali burn to the central cornea. It also showed that when treated with D-Dex, the CCT was lower than in untreated control eyes. Additionally, the amount of corneal neovascularization was lower in D-Dex treated eyes. These findings suggest that dendrimers may be a potential drug delivery platform in inflammatory ocular surface disorders especially because they target immune effector cells.
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